The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor: Outcomes and successful predictors of ITI treatment

INTRODUCTION:Immune tolerance induction ( ITI) was the primary therapeutic approach to eradicate inhibitors in haemophiliapatients. Several large ITIregistries had been reported, but successful predictors of ITIoutcome are still debated. No reports are available on large ITIstudies in non-caucasian countries. AIM:We designed a retrospective cohort study of ITIin Japanese haemophiliapatients with inhibitor. METHODS:Retrospective data were collected from 155 haemophilia(H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITIoutcome was centrally reviewed. We defined "success" as undetectable inhibitor after 2 consecutive measurements. RESULTS:The ITIsuccess rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITIusing von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITIwas a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). CONCLUSION:The results provided potentially important information for improving future success rates for ITIin inhibitor patients.